The Drug Discovery and Synthetic Chemistry Core of the CTT will take advantage of the resources of the MUSC Drug Discovery Center (DDC) to support all four projects in the CTT COBRE. The purpose of the DDC is to facilitate academic drug discovery efforts, to prepare new chemical entities for submission of an Investigational New Drug application, and to translate basic research results into the clinic. The DDC characterizes biological targets discovered by faculty researchers; identifies, synthesizes and optimizes lead compounds, and performs in vitro and in vivo studies that will support an IND application. The DDC closely collaborates with faculty researchers to develop high-throughput assays, and maintains a commercial collection of 50,000 compounds to be tested in these assays. The center conducts the actual screening process and analyzes data using in-house computational methods. Novel compounds identified through this process can be synthesized, and the resulting synthetic pathway used to produce analogues that have optimal efficacy and pharmacokinetic profiles. The DDC can then scale up optimized compounds for advanced pre-clinical studies. The DDC works with associated core facilities throughout MUSC and affiliated universities, and ultimately makes use of the clinical trial network available on the MUSC campus. The Center is also promoted throughout the region, with the expectation that pharmaceutical companies and small biotech companies will make use of the DDC drug development facility for screening, medicinal chemistry or pharmacokinetic analysis. The DDSC Core will pursue the following Specific Aims: 1) to provide synthetic chemistry support to the projects described in this COBRE application by designing de novo syntheses for potential target molecules, and to use these synthetic routes to introduce chemical diversity with the goal of lead optimization (Projects 1-4); 2) to provide rapid, automated screening services for de novo discovery of active compounds and screening of serial derivatives. Both general screens of a large commercial library and focused screens of chemically related congeners will be available (Projects 1-3); 3) to provide in silico support for all drug discovery efforts described in this proposal. This will include lead generation through virtual screening of publicly available databases of small, druggable molecules, and analysis of drug/biomolecular interactions to suggest rational structural changes that will enhance activity. Projects 2 and 3 will take immediate advantage of these services.